Probiotics alter the antibiotic resistance gene reservoir along the human GI tract

Antimicrobial resistance poses a substantial threat to human health. The gut microbiome is considered a reservoir (the gut “resistome”) for potential spread of resistance genes from commensals to pathogens. The impact of probiotics, commonly consumed by many in health or in conjunction to antibiotics administration, on the gut resistome remains elusive. Direct assessment of the gut resistome in situ along the gastrointestinal tract in healthy antibiotics-naïve humans supplemented with an 11-probiotic-strain preparation demonstrated that probiotics reduce the number of antibiotic resistance genes exclusively in the gut of colonization-permissive individuals. In mice and in a separate cohort of humans, a course of antibiotics resulted in expansion of the lower gastrointestinal (GI) tract resistome, which was mitigated by autologous fecal microbiome transplantation or during spontaneous recovery. In contrast, probiotics further exacerbated resistome expansion in the GI mucosa, by supporting the bloom of strains carrying vancomycin resistance genes, but not resistance genes encoded by the probiotic strains. Importantly, the aforementioned effects were not reflected in stool samples, highlighting the importance of direct sampling for analyzing the effect of probiotics and antibiotics on the gut resistome. Analyzing antibiotic resistance genes content in additional published clinical trials with probiotics further highlighted the importance of per-person metagenomics-based profiling of the gut resistome using direct sampling. Collectively, these findings suggest opposing person-specific and antibiotics-dependent effects of probiotics on the resistome, whose contribution to the spread of antimicrobial resistance genes along the human gastrointestinal tract merit further studies.